PROJECT SUMMARY ? NEUROPATHOLOGY CORE (CORE D) The UCI ADRC Neuropathology (NP) Core provides autopsy, diagnostic, and biorepository services for the three cohorts of the UCI ADRC - Uniform Data Set (UDS), 90+, and Down syndrome - which span a broad range of ages and susceptibilities to AD. The overarching goal of the NP Core is to support education, outreach, and research on AD and related disorders (ADRD) in collaboration with other ADRC cores and ADRD researchers to ?identify, quantify, and validate factors that influence the risk of AD across the lifespan.? Since its inception, the NP Core has collected and maintained a considerable bank of high-quality biospecimens, which have been distributed broadly to NCRAD and federally-funded local, national, and international ADRD investigators and consortia. Core operations have been continually enhanced, and metrics of core performance are strong. To expand its capacity, three new faculty have joined the NP Core, including a neuropathologist who is also a REC mentee (Mari Perez-Rosendahl). Together with the other UCI ADRC Cores, the NP Core proposes six Aims to enhance its diagnostic, education, and research functions via collaboration, innovation, and education: 1) Provide accurate, timely, comprehensive, and standardized postmortem examinations and diagnostic reports on UDS subjects and special populations, including the addition of postmortem skin collection on selected cases in collaboration with the iPSC Core; 2) Harvest, process, store, catalog, and distribute high-quality brain tissue and biospecimens to ADRD researchers at UCI and beyond, collaborating with the DMS and Biomarker Cores in its data management and biospecimen utilization functions; 3) Incorporate new analysis methods to enable novel microglial studies by UCI investigators at the cutting-edge of a new microglial biology in AD; 4) Incorporate whole slide imaging (WSI) to facilitate diagnoses, research, and education, including the establishment of interfaces with a UC-wide WSI network and UCI artificial intelligence (AI) center; 5) Support novel ADRD research and outreach in collaboration with other UCI ADRC Cores and other ADRCs, including new studies involving postmortem MRI, light sheet microscopy of cleared brain tissues, and AI studies of WSIs; and 6) Contribute unique expertise to the education and training of the next generation of AD clinicians and researchers, including Dr. Perez- Rosendahl, neuropathologist and REC mentee.